Streptococcus pneumoniae induces expression of the antibacterial CXC chemokine MIG/CXCL9 via MyD88-dependent signaling in a murine model of airway infection.

MIG/CXCL9 belongs to the CXC family of chemokines and participates in the regulation of leukocyte-trafficking and angiogenesis. Certain chemokines, including human MIG/CXCL9, exert strong antibacterial activity in vitro, although the importance of this property in vivo is unknown. In the present study, we investigated the expression and a possible role for MIG/CXCL9 in host defense during mucosal airway infection caused by Streptococcus pneumoniae in vivo. We found that intranasal challenge of C57BL/6 wild-type mice with pneumococci elicited production of high levels of MIG/CXCL9 in the lungs via the MyD88-dependent signaling pathway. Whereas both human and murine MIG/CXCL9 showed efficient killing of S. pneumoniae in vitro, MIG/CXCL9 knock-out mice were not more susceptible to pneumococcal infection. Our data demonstrate that, in vivo this chemokine probably has a redundant role, acting together with other antibacterial peptides and chemokines, in innate and adaptive host defense mechanisms against pneumococcal infections

a comprehensive approach to adrenal incidentalomas

Improvements in abdominal imaging techniques have increased the detection of clinically inapparent adrenal masses, or incidentalomas (AI), the appropriate diagnosis and management of which have become a common clinical problem for health care professionals. Once an adrenal mass has been detected, the clinician needs to address two questions: 1) is the tumor hormonally active? and 2) is there any chance of the mass being malignant? The majority of AI is non-hypersecretory cortical adenomas, but an endocrine evaluation can lead to the identification of subtle hormone excess. An overnight low-dose dexamethasone suppression test, fractionated urinary or plasma metanephrine assay and, in hypertensive patients, establishing the upright plasma aldosterone/plasma renin activity ratio are recommended as preliminary screening steps. Masses greater than 4cm are at greater risk of malignancy. Morphological imaging features may be helpful in the distinction between benign and malignant forms. Fine-needle aspiration biopsy is an important tool in the evaluation of oncological patients to establish any metastatic disease. Adrenalectomy is indicated by evidence of a functional adrenal mass, or a suspected malignant form. We advocate adrenalectomy of subtle hypercortisolism, especially in the presence of hypertension, obesity, diabetes or osteoporosis potentially aggravated by glucocorticoid excess. A close follow-up is needed, particularly in the first year after diagnosis

Structure-Activity Studies and Therapeutic Potential of Host Defense Peptides of Human Thrombin

Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length-and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (> 12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest

Corticotropin-releasing hormone test predicts the outcome of unilateral adrenalectomy in primary bilateral macronodular adrenal hyperplasia

Purpose: Primary bilateral adrenal hyperplasia (PBMAH) is associated with hypercortisolism and a heterogeneous clinical expression in terms of cortisol secretion and related comorbidities. Historically, treatment of choice was bilateral adrenalectomy (B-Adx); however, recent data suggest that unilateral adrenalectomy (U-Adx) may be an effective alternative. For the latter, factors predicting the postsurgical outcome (e.g., biochemical control) have not been identified yet. Methods: PBMAH patients undergoing U-Adx for overt Cushing's syndrome (CS) in two tertiary care centers were retrospectively analysed. Remission was defined as a normalization of urinary free cortisol (UFC) without the need for medical treatment. The potential of hCRH test as a predictor of U-Adx outcome was evaluated in a subgroup. Results: 23 patients were evaluated (69% females, mean age 55 years). Remission rate after U-Adx was 74% at last follow up (median 115 months from UAdx). Before U-Adx, a positive ACTH response to hCRH (Δ¬TH increase > 50% from baseline) was associated with higher remission rates. Conclusions: Three of four patients with PBMAH are surgically cured with U-Adx. Pre-operative hCRH testing can be useful to predict long-term remission rates

Cyclic Cushing's syndrome: an overview

Cyclic Cushing's syndrome (CS) is a disorder in which glucocorticoid levels are alternately normal and high, the latter occurring in episodes that can last from a few days to several months. It is more common in children than in adults. Cyclic CS may be either of the two different forms of CS (ACTH-dependent or -independent CS). Clinically, it may present with one or many symptoms, depending on the duration of disease activity and the timing of the fluctuations. A serotoninergic influence, cyclic changes in central dopaminergic tone, spontaneous episodic hemorrhage in the tumor, and the action of inflammatory cytokines with antitumor properties are some of the mechanisms suggested to explain the physiopathology of this phenomenon but the exact mechanism remains to be clarified. The cyclic pattern of hypercortisolism can delay the final diagnosis of CS and make it difficult to interpret the results of dynamic tests. Patients may have paradoxical responses to dexamethasone that can reflect increasing or decreasing levels of endogenous activity. Hormone assessments have to be repeated periodically when a diagnosis of CS is suspected. The cyclic pattern can also interfere with medical treatment because patients may show unexpected clinical and biochemical signs of hypocortisolism when cortisol secretion cyclically returns to normal, so an accurate follow-up is mandatory in these patients

Carbapenemase-producing Enterobacteriaceaein Europe: assessment by national experts from 38 countries, May 2015

European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) working group collaborators: Koraqi A, Bino S, Hartl R, Apfalter P, Glupczynski Y, Jans B, Marković T, Dedeić- Ljubović A, Kojić D, Strateva T, Sabtcheva S, Butić I, Andrašević AT, Pieridou-Bagatzouni D, Panayiota M, Hrabák J, Žemličková H, Hammerum AM, Skov R, Ivanova M, Jalava J, Dortet L, Vaux S, Kaase M, Eckmanns T, Vatopoulos A, Giamarellou H, Tóth Á, Kurcz A, Hardarson H, Kristinsson K, Boo TW, Burns K, Carmeli Y, Pantosti A, Kurti A, Raka L, Balode A, Miciulevičienė J, Valintėlienė R, Perrin-Weniger M, Nestorova N, Borg M, Mijović G, Mugosa B, Meessen N, de Greeff S, Samuelsen Ø, Simonsen GS, Żabicka D, Hryniewicz W, Caniça M, Paiva JA, Kaftandzieva A, Memeti S, Damian M, Codita I, Jelesić Z, Stevanovic G, Nikš M, Schréterová E, Pirš M, Kolman J, Oteo J, Campos J, Giske CG, Sjöström K, Gür D, Ekmekci E, Wiuff C, Hopkins K, Woodford N, Cantón R, Friedrich AW, Gniadkowski M, Poirel L, Rossolini GM, Seifert H, Walsh T, Livermore D, Nordmann P.In 2012, the European Centre for Disease Prevention and Control (ECDC) launched the 'European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE)' project to gain insights into the occurrence and epidemiology of carbapenemase-producing Enterobacteriaceae (CPE), to increase the awareness of the spread of CPE, and to build and enhance the laboratory capacity for diagnosis and surveillance of CPE in Europe. Data collected through a post-EuSCAPE feedback questionnaire in May 2015 documented improvement compared with 2013 in capacity and ability to detect CPE and identify the different carbapenemases genes in the 38 participating countries, thus contributing to their awareness of and knowledge about the spread of CPE. Over the last two years, the epidemiological situation of CPE worsened, in particular with the rapid spread of carbapenem-hydrolysing oxacillinase-48 (OXA-48)- and New Delhi metallo-beta-lactamase (NDM)-producing Enterobacteriaceae. In 2015, 13/38 countries reported inter-regional spread of or an endemic situation for CPE, compared with 6/38 in 2013. Only three countries replied that they had not identified one single case of CPE. The ongoing spread of CPE represents an increasing threat to patient safety in European hospitals, and a majority of countries reacted by establishing national CPE surveillances systems and issuing guidance on control measures for health professionals. However, 14 countries still lacked specific national guidelines for prevention and control of CPE in mid-2015

European Antibiotic Awareness Day: a five-year perspective of Europe-wide actions to promote prudent use of antibiotics.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Following the European Union (EU) Council Recommendation on prudent use of antimicrobial agents in human medicine in 2001, and the success of national campaigns, i.e. Belgium and France, the European Centre for Disease Prevention and Control (ECDC) decided to establish the European Antibiotic Awareness Day (EAAD) on 18 November as platform to support national campaigns across Europe. This article provides an overview of EAAD tools, materials, and activities developed during the first five years. It shows that EAAD has been successful due to good cooperation between ECDC and national institutions, strong political and stakeholder support and evidence-based development of campaign materials. EAAD has provided a platform for pre-existing national campaigns and encouraged similar campaigns to develop where neither political support had been secured, nor financial support had been available. As a result, participating countries have continuously expressed strong support for ECDC to continue its work on EAAD. This has been endorsed by a steadily increasing number of countries participating and the growing interest of varied professional and stakeholder organisations. We conclude that EAAD should continue to act as catalyst for discussion and as mechanism to raise awareness of the public and prescribers about prudent use of antibiotics

Windenergie-Nutzung

Innerhalb des Gesamtrahmens des Projektes "Klimaverträgliche Energieversorgung in Baden-Württemberg" ist es das Ziel des Gutachtens über die Windenergienutzung, die Möglichkeiten und Grenzen einer windtechnischen Stromerzeugung in Baden-Württemberg darzustellen und zu diskutieren. Gleichzeitig sollen die notwendigen technischen, ökonomischen, ökologischen und sonstigen Eckdaten für die in der zweiten Projektphase geplante Szenarioanalyse, deren Ausgangspunkt die politische Orientierung der CO2-Emissionsminderung um 30% im Zeitraum von 1987 bis 2005 ist, zur Verfügung gestellt werden

The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp(-) somatotropinomas

Glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion of gsp(-) somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load

Worsening epidemiological situation of carbapenemase-producing Enterobacteriaceae in Europe, assessment by national experts from 37 countries, July 2018

European Antimicrobial Resistance Genes Surveillance Network (EURGen-Net) capacity survey group (Portugal): Manuela Caniça, Vera Manageiro,A survey on the epidemiological situation, surveillance and containment activities for carbapenemase-producing Enterobacteriaceae (CPE) was conducted in European countries in 2018. All 37 participating countries reported CPE cases. Since 2015, the epidemiological stage of CPE expansion has increased in 11 countries. Reference laboratory capability, dedicated surveillance and a specific national containment plan are in existence in 33, 27 and 14 countries, respectively. Enhanced control efforts are needed for CPE containment in Europe.info:eu-repo/semantics/publishedVersio